Fig 13.1A from Sadler (2006). Langman’s Medical Embryology, 10 th ed.
Left figure: Fig 11-4 from Schoenwolf et al. (2009). Larsen’s Human Embryology, 4 th ed. Right figure: Fig 13.3 from from Sadler (2006). Langman’s Medical Embryology, 10 th ed.
Left: Fig 13.6A Right: Fig 13.7
Schoenwolf et al: Larsen’s Human Embryology, 4 th Edition. Copyright 2008 Churchill Livingston, an imprint of Elsevier, Inc. All rights reserved
Carlson: Human Embryology and Developemental Biology, 4 th Edition. Copyright 2009 by Mosby, an imprint of Elsevier, Inc. All rights reserved.
Embrology of the respiratory system
By ORIBA DAN LANGOYA
The lung buds form during the 4th
Initially appear as the respiratory diverticulum, which is a ventral
outgrowth of foregut endoderm
MESODERM dependent process.
Langman’s Medical Embryology, 10th
The respiratory tract is derived from foregut endoderm
and associated mesoderm
epithelial lining of trachea,
larynx, bronchi, alveoli
From splanchnic mesoderm:
cartilage, muscle, and
connective tissue of tract
and visceral pleura.
Splitting of foregut into esophagus and trachea
Tracheo-esophageal ridges: longitudinal ridges that
eventually fuse to separate trachea from esophagus.
Incomplete separation and/or atresia of trachea and esophagus (B on right shows esophageal atresia)
Defect likely in mesoderm and usually associated with other defects involving mesoderm (cardiovascular
malformations, VATER / VACTERL, etc.)
VATER = Vertebral anomalies, Anal atresia, Tracheoesophageal fistula, Esophageal atresia, Renal atresia
VACTERL = VATER + Cardiac defects & Limb defects
Tracheoesophageal Fistulas / Esophageal Atresia
Occur in approx 1/3000 births, most (90%) are that shown in (A)
PRENATAL: Polyhydramnios (due to inability to swallow amniotic fluid in utero)
Gastrointestinal: Infants cough and choke when swallowing because of accumulation of
excessive saliva in mouth and upper respiratory tract. Milk is regurgitated immediately after
Respiratory: Gastric contents may also reflux into the trachea and lungs, causing choking and
often leading to pneumonitis.
Successive stages in the development of the larynx:
The epithelial lining of the larynx is of endodermal origin. The
cartilages and muscles of the larynx arise from mesenchyme from the
4th and 6th pharyngeal arches
This rare anomoly results in obstruction of the upper
airway - congenital high airway obstruction syndrome
This uncommon anomaly results from incomplete
recanalization of the larynx during the 10th week. A
membranous web forms at the level of the vocal cords,
partially obstructing the airway
14 weeks - photomicrograph
Progressive changes in the development of the laryngotracheal tube:
Endodermal lining distal to the larynx differentiates into the epithelium and
glands of the trachea and pulmonary epithelium. The cartilage, connective
tissue and muscles of the trachea derive from splanchnic mesenchyme.
Differentiation of pleural membranes
The lung buds “punch” into the visceral mesoderm. The mesoderm, which covers the
outside of the lung, develops into the visceral pleura. The somatic mesoderm,
covering the body wall from the inside, becomes the parietal pleura. The space
between is the pleural cavity.
Pleuropericardial folds separate
pleural and pericardial cavities.
5 weeks - pleuropericardial fold
8 weeks - lungs grow and
expand into pleural cavity
6 weeks - pleuropericardial
membrane reaches midline
7 weeks -further maturation of
pericardium (expands pleural cavity
Separating the abdominal and thoracic cavities:
development of the septum transversum and diaphragm
The septum transversum stops at the gut tube, leaving two open passageways on the left and
right sides, the “pericardioperitoneal canals” (shown on the left)
Closing off these canals requires growth from the dorsolateral body wall, aka the
“pleuroperitoneal membranes” (shown on the right)
Defects in this process cause CDH (congenital diaphragmatic hernias): abdominal contents
herniate into pleural cavities and interfere with lung development.
First three branching events are
After the initial bifurcation into
two primary bronchi, two buds, or
secondary bronchi, form on the
left and three on the right
predicting the five lobes of the
adult human lung. Ten tertiary
(segmental) bronchi form in the
right lung and eight in the left
lung - establishing the
brochopulmonary segments of
the adult human lung.
Initial Patterning of the Lung:
Stages of Maturation of the Lungs
Period (5-17 weeks):
By 17 weeks, all major
elements have formed,
except those involved with
gas exchange (fetuses
unable to survive if born at
Bronchi, terminal bronchioles
become larger, lung tissue
becomes highly vascular.
Alveolar ducts form by week
24. By end, some terminal
sacs have formed so
respiration is possible (small
chance of survival at this
Period (24 weeks
Many more terminal sacs
develop, their epithelium
becomes very thin and
capillaries bulge into the
(By 26-28 wks, 1000 gr
fetus has a sufficient # of
sacs and surfactant to
Alveolar Period (late
fetal period to age 8):
Alveoli-like structures are
present by 32 weeks. Epithelial
lining of sacs attenuate to
extremely thin squamous
epithelia, capable of gas
exchange. 95% of
characteristic, mature alveoli
develop after birth.
Surfactant proteins augment function of phospholipid
Four major surfactant proteins: A, B, C, and D
Surfactant A: activates macrophages to elicit uterine contractions, also important in host defense
Surfactant B: organizes into tubular structures that are much more efficient at reducing surface
tension (specific deficiency in Surfactant B can lead to respiratory distress)
Surfactant C: enhances function of surfactant phospholipids
Surfactant D: important in host defense.
This disease affects 2% of live
newborn infants, with
prematurely born being most
susceptible. 30% of all
neonatal disease results from
HMD or its complications.
Surfactant deficiency is the major cause of RDS or HMD. The lungs are underinflated and the alveoli
contain a fluid of high protein content, probably derived from circulation substances and injured pulmonary
In addition to prematurity, prolonged intrauterine asphyxia may produce irreversible changes in Type II
alveolar cells, rendering them incapable of producing surfactant. Other factors may contribute to surfactant
deficiency, but the genetics of surfactant production are not well-defined.
Prolonged, labored breathing damages alveolar epithelium, leading to protein deposition, or “hyaline”
changes (shown in figure).
Congenital Lung Cysts:
Cysts (filled with fluid or air) are thought to be formed by the
dilation of terminal bronchi, probably due to irregularities in
later development. If severe, cysts are visible on
radiographs. Highly variable outcomes result from different
Agenesis of the Lungs:
Can occur bilaterally or unilaterally. Unilateral lung
agenesis is compatible with live as remaining side
hyperexpands and compensates.
Often caused by congenital diaphragmatic hernias or
congenital heart disease. Characterized by reduced lung
volume. Extreme hypoplasia is inconsistent with life.